Loss of heterozygosity analysis of 13q and 14q in human malignant mesothelioma

Cytogenetic investigations of malignant mesothelioma (MM) have revealed fre quent losses in chromosomes 13 and 14, suggesting that inactivation of tumo r suppressor genes (TSGs) residing in these chromosomes may contribute to m esothelial cell tumorigenesis. To define the shortest region of overlap (SR O) of deletions from these chromosomes, we performed loss of heterozygosity (LOH) analyses on 30 MMs using 25 microsatellite markers in 13q and 21 mar kers in 14q. Twenty of the 30 MMs (67%) showed allelic loss of at least one marker in 13q. The SRO of deletions was delineated as an similar to 7 cent iMorgan region, flanked by markers D 13S 1253 and D 13S291, located at 13q 13.3-14.2. Thirteen of the 30 MMs (43%) displayed allelic losses from 14q, with at least three distinct regions of LOH located at segments q 11.2- 13. 2, q22.3-24.3, and q32. 12. These data highlight a single region of chromos omal loss in 13q in many MMs, implicating the involvement of a TSG that is critical to the pathogenesis of this malignancy. In contrast, the lower inc idence and diffuse pattern of allelic losses in 14q suggest: that several T SGs in this chromosome arm may contribute to tumorigenic progression in a s ubset of MMs. (C) 2000 Wiley-Liss, Inc.